{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:06:43Z","timestamp":1787314003842,"version":"build-2736575974"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      The aim of this study was to assess the prevalence of human epidermal growth factor receptor 2 (HER2) protein expression and\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      gene amplification in a large cohort of tumor samples from patients with advanced urothelial carcinoma (UC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Testing was performed on formalin-fixed, paraffin-embedded tissue from commercially sourced primary advanced or metastatic UC using an anti-HER2\/neu (4B5) rabbit monoclonal antibody immunohistochemistry (IHC) assay (detects HER2 protein) and HER2 dual in situ hybridization (DISH) DNA probe cocktail assay (detects\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      gene and the centromere of its residing chromosome 17). The HER2 clinical status was classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+\/DISH nonamplified), or HER2-positive (IHC 2+\/DISH amplified or IHC 3+).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Of the 2,024 UC samples, HER2 protein expression was IHC 0 for 962 (47.5%), IHC 1+ for 297 (14.7%), IHC 2+ for 498 (24.6%), and IHC 3+ for 267 (13.2%). The percentage of HER2-expressing tumors (IHC 1+, 2+, and 3+) was similar between primary (52.2%, 1,028\/1,968) and metastatic UC samples (60.7%, 34\/56;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .26). The\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      gene was amplified in 235 cases (11.6%), including 2.7%\/3.7%\/9.6%\/56.2% scored as IHC 0\/1+\/2+\/3+, respectively. Overall, HER2 clinical status was HER2-zero for 962 UC tissue samples (47.5%; 95% CI, 45.4 to 49.7), HER2-low for 747 (36.9%; 95% CI, 34.8 to 39.0), and HER2-positive for 315 (15.6%; 95% CI, 14.0 to 17.2).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      We observed that more than 50% of 2,024 advanced UC tumors demonstrated some degree of HER2 protein expression detected using a standardized IHC method, whereas about 12% of specimens had\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      gene amplification, including about 3% of those scored as either IHC 0 or 1+. Continued development of optimized and standardized HER2 testing methods is warranted to identify patients with HER2-expressing UC who may benefit from novel HER2-targeting therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-24-00879","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T15:59:17Z","timestamp":1744819157000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Testing and Interpretation of Human Epidermal Growth Factor Receptor 2 Protein Expression and\n                    <i>ERBB2<\/i>\n                    Gene Amplification in Advanced Urothelial Carcinoma"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-8668","authenticated-orcid":true,"given":"Vadim S.","family":"Koshkin","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-5621","authenticated-orcid":true,"given":"Johanna M.","family":"Schafer","sequence":"additional","affiliation":[{"name":"Roche Diagnostics Solutions, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Scherrer","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Bothell, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Boyiddle","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Bothell, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-7801","authenticated-orcid":true,"given":"Naomi R.M.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Bothell, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yu","sequence":"additional","affiliation":[{"name":"Pfizer Inc, Bothell, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijun","family":"Fang","sequence":"additional","affiliation":[{"name":"Roche Diagnostics Solutions, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda F.","family":"Baker","sequence":"additional","affiliation":[{"name":"Roche Diagnostics Solutions, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh H.","family":"Sayedian","sequence":"additional","affiliation":[{"name":"Roche Diagnostics Solutions, Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-4004","authenticated-orcid":true,"given":"Emily","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-2488"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2022.102351"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-022-04459-7"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02005"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00621-0"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.4570"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2003.08.027"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(03)00067-2"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp488"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043720"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1011885"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.5740"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29826"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.007"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.08.005"},{"key":"e_1_3_8_17_2","unstructured":"National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Bladder cancer version 5.2024. https:\/\/www.nccn.org"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqab083"},{"key":"e_1_3_8_19_2","article-title":"Comprehensive analysis of human epidermal growth factor receptor 2 through DNA, mRNA, and protein in diverse malignancies","author":"Shayeb AM","unstructured":"Shayeb AM, Kurzrock R, Adashek JJ, et al: Comprehensive analysis of human epidermal growth factor receptor 2 through DNA, mRNA, and protein in diverse malignancies. 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